Atopic Dermatitis, Atopic Disorders, Atopic Eczema, Eczema
Conditions
Keywords
Prevention, Emollient, Pragmatic clinical trial
Brief summary
Atopic dermatitis (AD) affects over 9 million children in the U.S. and often heralds the development of asthma, food allergy, skin infections and neurodevelopmental disorders. Recent advances identify skin barrier dysfunction to be the key initiator of AD and possibly allergic sensitization. Our central hypothesis is that daily emollient use from birth can prevent the development of AD in a community setting and into newborns unselected for risk. The results of a community-based clinical trial utilizing a pragmatic trial design will be immediately applicable to the population at large and will establish a new standard of care for all newborns.
Detailed description
AD affects over 9 million children in the U.S. and ranks first among all skin conditions in global disability burden. AD often heralds the development of several comorbidities including asthma, food allergy, skin infections and neurodevelopmental disorders. Because of the significant socioeconomic impact of atopic dermatitis and its effect on the quality of life of children and families, there have been decades of research focused on prevention with limited success. Recent advances in cutaneous biology identify epidermal defects and skin barrier dysfunction to be the key initiators of atopic dermatitis and possibly allergic sensitization. Our central hypothesis is that emollient therapy from birth can prevent the development of AD. The findings of this trial will support the development of evidence-based skin care clinical guidelines for infants that currently do not exist. Recently, our international multi-centered clinical trial found enhancing early skin barrier function with daily emollient use from birth significantly reduces the risk of AD development in high-risk populations by 50%. With CASCADE, we extend this work into the community setting and into newborns unselected for risk, so results will be immediately applicable to the population at large and will establish a new standard of care for all newborns. The specific aims are as follows: 1. Perform a community-based pragmatic randomized controlled trial investigating whether daily full-body emollient application starting in the first 2 months of life prevents atopic dermatitis in a real-world setting. The population for this trial consists of newborns between 0-2monthsof age, not selected for risk. Recruitment of families will occur during the course of routine care within primary care offices that are members of practice-based research networks(PBRNs).The intervention includes general skin care recommendations plus full-body daily lipid-rich emollient use. The control population will receive general skin care advice only and refrain from daily emollient use. The primary outcome will be the cumulative incidence of atopic dermatitis at age 24 months as determined by blinded clinicians trained in the diagnosis of AD. Key secondary clinical outcomes include time to disease onset and incidence of self-reported food allergy and wheeze using parental questionnaires. 2. As an exploratory aim, determine whether a family history of allergic disease and key early life exposures such as pet ownership modify the preventive effect of emollient therapy on atopic dermatitis. While the primary objective of this clinical trial is to determine the effectiveness of an emollient intervention in a real-world setting, data will be gathered on allergy history in the family and pet ownership-variables that may modify the effect of emollient therapy. Future implementation studies may target subpopulations found most likely to benefit from emollient intervention. Twenty-five primary care clinics that participate in PBRNs from Oregon, Colorado, Wisconsin and North Carolina are the setting for the study protocol. The expected results from this project would represent a major public health breakthrough with the potential for reducing the atopic disease burden on a global scale.
Interventions
OTHERParticipant choice of over-the-counter emollients: Vaseline, Vanicream, CeraVe Healing Ointment, CeraVe cream, Cetaphil cream
Lipid-rich emollient serving as skin barrier
Sponsors
University of Wisconsin, Madison
University of Colorado, Denver
Duke University
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Oregon Health and Science University
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
TRIPLE (Caregiver, Investigator, Outcomes Assessor)
Masking description
Due to the nature of the intervention, it is not possible blind dyads to the intervention. Administering a placebo emollient is impossible as there are no active ingredients in the emollient and using an emollient that has no barrier improvement properties may irritate the skin. The clinician completing the final assessment will be a blinded assessor. Clinic staff will not be informed of participant enrollment or study arm. Parents will be instructed not to disclose their treatment group to clinic staff. Clinicians and clinic staff will direct participants to follow skin care recommendations as described by the study materials. Blinded researchers will be responsible for health record review to collect the primary outcome. At completion of health record review, researchers will complete a form measuring whether the assessor became unblinded while reviewing the record.
Intervention model description
This is a pragmatic, multi-site, randomized community-based trial in which dyads of a parent or legal guardian (parent) and an infant age 0 to 2 months are enrolled. Participating dyads are randomly assigned to receive lipid-rich emollient with web-based instructions for daily use to infants plus routine skin care instructions (every day moisturizer group) or routine skin care instructions alone (natural skin group). Both groups will receive e-mail and text message reminders to follow protocol instructions based on their group allocation until the infant reaches 24 months old.
Eligibility
Sex/Gender
ALL
Age
1 Days to 63 Days
Healthy volunteers
Yes
Inclusion criteria
* Parent can provide electronic signed and dated informed consent form. * Parent is willing and able to comply with all study procedures for the duration of the study. * Parent is a primary caretaker of an infant 0 to 2 months of age. * Parent is 18 years of age or older at time of consent. * Parent can speak, read, and write in English or Spanish. * Parent has a valid e-mail address or phone that can receive text messages * Parent has reliable access to the internet. * Infant is a patient of a participating Meta-LARC clinic site at the time of consent.
Exclusion criteria
* Infant was born at less than 25 weeks gestational age. * Infant has established eczema as diagnosed by the primary healthcare provider at clinic site of enrollment per parent report. * Infant has known adverse reaction to petrolatum-based emollients. * Infant has an immunodeficiency genetic syndrome such as Wiskott-Aldrich Syndrome or Severe Combined Immunodeficiency Syndrome. * Infant has extremely low birth weight (less than 1000g or 2.2 lbs at birth). * Infant has a sibling enrolled in the study. * Parent is unwilling or unable to comply with study procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Provider-diagnosed Atopic Dermatitis | up to 24 months | The cumulative incidence of AD as recorded in health records. Trained clinicians will assess for AD at each clinic visit and record in the health record. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Parent Report of Atopic Dermatitis | up to 24 months | Parent or guardian reports that a clinician has diagnosed their child with atopic dermatitis (eczema) at any quarterly contact up to 24 months of age. |
| Atopic Dermatitis by UK Working Party Criteria | up to 24 months | Parental report of AD using UK Working Party criteria. Parent responds yes to all parts of a modified version of the UK Working Party criteria at 12 and/or 24 month. Criteria include an itchy rash in flexural areas, generally dry skin, and asthma or hay fever in a first-degree relative. |
| Atopic Dermatitis by Children's Eczema Questionnaire | up to 24 months | AD as diagnosed by the Children's Eczema Questionnaire (CEQ). Parent response to 3 CEQ questions is consistent with AD at 12 and/or 24 months of age. |
| Atopic Dermatitis With Prescription or Over-the-counter Therapies in Chart | up to 24 months | Cumulative incidence of provider-diagnosed AD requiring prescription or over-the-counter therapies from chart review. Health records at primary care practice includes both a diagnosis of AD and prescription and/or over-the-counter (OTC) therapies. Prescription therapies could be steroids, calcineurin inhibitors, crisaborole, or antibacterials. OTC therapies could be steroids or antihistamines. |
| Atopic Dermatitis With or Without Prescription or Over-the-counter Therapies in Chart (Ordinal) | Up to 24 months | Ordinal coding of diagnosis of atopic dermatitis (eczema) in primary care health records, coded as none, eczema without prescription or over-the-counter (OTC) topical therapies, eczema with OTC only, or eczema with prescription therapies. Prescription therapies could be steroids, calcineurin inhibitors, crisaborole, or antibacterials. OTC therapies could be steroids or antihistamines. |
| Prescribed or Over-the-counter Topical Skin Medication by Parent Report | up to 24 months | Ordinal formulation of parent report: no AD, AD not treated with steroidal or non-steroidal cream or ointment (therapy), AD treated with over-the-counter (OTC) therapy, AD treated with prescription therapy. AD could be reported on annual questionnaires or quarterly contacts. Therapies reported on annual questionnaires. |
| Skin Infections Diagnosed and Recorded in Chart Review | up to 24 months | Chart outcome for provider diagnosis or medications associated with skin infections, including topical antibiotics. Skin infection diagnoses include impetigo, candida, wart/verruca, molluscum, or herpes simplex. |
| Primary Outcome of Provider-diagnosed Atopic Dermatitis | up to 12 months | Diagnosis of atopic dermatitis (eczema) recorded by primary care providers in health records up to 12 months of age (rather than 24 months). |
| Provider-diagnosed Atopic Dermatitis at 18 Months | up to 18 months | Diagnosis of atopic dermatitis (eczema) recorded by primary care providers in health records up to 18 months of age. |
| Provider-diagnosed Asthma | up to 24 months | Health records at primary care practice include at least one diagnosis of asthma. |
| Severity of AD Symptoms Using POEM | 12 months of age | Patient-Oriented Eczema Measure (POEM) score, elicited from families of infants who reported AD diagnosis at this or any previous contact or whose CEQ response indicated AD. The POEM has seven items and ranges from 0 to 28, with higher scores reflecting more severe symptoms of AD. |
| Severity of AD Symptoms Using IDQoL | 12 months | Symptom severity as reflected by the Infant Dermatology Quality of Life Instrument (IDQoL) elicited from families of infants who reported AD diagnosis at this or any previous contact or whose CEQ response indicated AD. The IDQoL has 12 items and ranges from 0-37 with higher scores reflecting greater adverse effect of AD on quality of life |
| Food Allergy Symptoms | 12 months, 24 months or both | Parent reports immediate food allergy reaction in child at 12- or 24-month questionnaire, or both. |
| Food Allergy Diagnosis With Positive Test | up to 24 months | Parent reports a provider diagnosis of and a positive test for food allergy at 12- or 24-month questionnaire, or both. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Provider-diagnosed Atopic Dermatitis - Low-risk Population | up to 24 months | Subgroup population: In the subgroup of participants who did not report atopic dermatitis in a first-degree relative, diagnosis of atopic dermatitis (eczema) recorded by primary care providers in health records |
| Provider-diagnosed Atopic Dermatitis - High-risk Population | up to 24 months | Subgroup population: In the subgroup of participants who reported atopic dermatitis in a first-degree relative, diagnosis of atopic dermatitis (eczema) recorded by primary care providers in health records |
Countries
United States
Participant flow
Recruitment details
Recruitment from 25 community-based primary care sites in four states (Oregon, North Carolina, Wisconsin, Colorado) from July 2018-February 2021.
Participants by arm
| Arm | Count |
|---|---|
| Daily Emollient Parents assigned to the intervention arm receive a lipid-rich emollient and educational materials promoting once daily full-body emollient use until infant age 24 months.
Participant choice of over-the-counter emollients: Vaseline, Vanicream, CeraVe Healing Ointment, CeraVe cream, Cetaphil cream: Lipid-rich emollient serving as skin barrier | 603 |
| Natural Skin Parents assigned to the control arm receive educational materials promoting general infant skin care guidelines only and to refrain from emollient use unless dry skin develops (current standard of care guidelines). | 625 |
| Total | 1,228 |
Baseline characteristics
| Characteristic | Natural Skin | Total | Daily Emollient |
|---|---|---|---|
| Age, Continuous | 24.0 Days STANDARD_DEVIATION 16.6 | 23.9 Days STANDARD_DEVIATION 16.3 | 23.9 Days STANDARD_DEVIATION 16 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 141 Participants | 285 Participants | 144 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 459 Participants | 896 Participants | 437 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 25 Participants | 47 Participants | 22 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 15 Participants | 13 Participants |
| Race (NIH/OMB) Asian | 16 Participants | 35 Participants | 19 Participants |
| Race (NIH/OMB) Black or African American | 41 Participants | 85 Participants | 44 Participants |
| Race (NIH/OMB) More than one race | 53 Participants | 112 Participants | 59 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 38 Participants | 65 Participants | 27 Participants |
| Race (NIH/OMB) White | 473 Participants | 912 Participants | 439 Participants |
| Sex/Gender, Customized Female | 274 Participants | 553 Participants | 279 Participants |
| Sex/Gender, Customized Male | 350 Participants | 674 Participants | 324 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 614 | 1 / 633 |
| other Total, other adverse events | 134 / 614 | 155 / 633 |
| serious Total, serious adverse events | 25 / 614 | 39 / 633 |
Outcome results
Primary
Provider-diagnosed Atopic Dermatitis
The cumulative incidence of AD as recorded in health records. Trained clinicians will assess for AD at each clinic visit and record in the health record.
Time frame: up to 24 months
Population: Diagnosis of atopic dermatitis recorded by primary care clinicians in health records by 24 (+/- 3) months of age. Multiple imputation of 199 missing outcomes (92 intervention, 107 control). All ITT with multiple imputation for participants with absent outcome data. Numbers represent participants per randomized arm, regardless of adherence to instructions. Counts were summarized over 15 multiple imputation datasets generated by chained equations using baseline and follow-up survey responses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daily Emollient | Provider-diagnosed Atopic Dermatitis | 217.7 Participants with imputed values |
| Natural Skin | Provider-diagnosed Atopic Dermatitis | 268.5 Participants with imputed values |
Comparison: The null hypothesis is that the cumulative incidence of atopic dermatitis does not differ between the Daily Emollient and Natural Skin arms, or that the risk ratio is equal to 1.p-value: 0.01995% CI: [0.73, 0.97]Regression, log-binomial
Secondary
Atopic Dermatitis by Children's Eczema Questionnaire
AD as diagnosed by the Children's Eczema Questionnaire (CEQ). Parent response to 3 CEQ questions is consistent with AD at 12 and/or 24 months of age.
Time frame: up to 24 months
Population: Multiple imputation of 136 outcomes considered missing when parent did not respond at 24 months and the previous 12-month contact was not positive for AD by these criteria. All ITT with multiple imputation for 11% of participants with absent outcome data. Numbers represent participants according to arm randomized, regardless of adherence to study instructions. Counts were summarized over 15 multiple imputation datasets generated by chained equations using baseline and follow-up survey responses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daily Emollient | Atopic Dermatitis by Children's Eczema Questionnaire | 156.9 Participants with imputed values |
| Natural Skin | Atopic Dermatitis by Children's Eczema Questionnaire | 195.3 Participants with imputed values |
Comparison: The null hypothesis is that the cumulative incidence of AD by CEQ does not differ between the Daily Emollient and Natural Skin arms, or that the risk ratio (RR) is equal to 1.p-value: 0.04495% CI: [0.7, 0.99]Regression, log-binomial
Secondary
Atopic Dermatitis by UK Working Party Criteria
Parental report of AD using UK Working Party criteria. Parent responds yes to all parts of a modified version of the UK Working Party criteria at 12 and/or 24 month. Criteria include an itchy rash in flexural areas, generally dry skin, and asthma or hay fever in a first-degree relative.
Time frame: up to 24 months
Population: Multiple imputation of 148 outcomes considered missing when parent did not respond at 24 months and the previous 12-month contact was not positive for AD by these criteria. All ITT with multiple imputation for 12% of participants with absent outcome data. Numbers represent participants according to arm randomized, regardless of adherence to study instructions. Counts were summarized over 15 multiple imputation datasets generated by chained equations using baseline and follow-up survey responses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daily Emollient | Atopic Dermatitis by UK Working Party Criteria | 72.3 Participants with imputed values |
| Natural Skin | Atopic Dermatitis by UK Working Party Criteria | 83.1 Participants with imputed values |
Comparison: The null hypothesis is that the cumulative incidence of AD by modified UK Working Party criteria does not differ between the Daily Emollient and Natural Skin arms, or that the risk ratio (RR) is equal to 1.p-value: 0.32395% CI: [0.65, 1.15]Regression, log-binomial
Secondary
Atopic Dermatitis With or Without Prescription or Over-the-counter Therapies in Chart (Ordinal)
Ordinal coding of diagnosis of atopic dermatitis (eczema) in primary care health records, coded as none, eczema without prescription or over-the-counter (OTC) topical therapies, eczema with OTC only, or eczema with prescription therapies. Prescription therapies could be steroids, calcineurin inhibitors, crisaborole, or antibacterials. OTC therapies could be steroids or antihistamines.
Time frame: Up to 24 months
Population: All ITT with multiple imputation for 16% of participants with absent outcome data. Numbers represent participants according to arm randomized, regardless of adherence to study instructions. Counts were summarized over 15 multiple imputation datasets generated by chained equations using baseline and follow-up survey responses.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Daily Emollient | Atopic Dermatitis With or Without Prescription or Over-the-counter Therapies in Chart (Ordinal) | No atopic dermatitis | 385.3 Participants with imputed values |
| Daily Emollient | Atopic Dermatitis With or Without Prescription or Over-the-counter Therapies in Chart (Ordinal) | Atopic dermatitis without topical medication | 101.2 Participants with imputed values |
| Daily Emollient | Atopic Dermatitis With or Without Prescription or Over-the-counter Therapies in Chart (Ordinal) | Atopic dermatitis with over-the-counter therapy | 38.3 Participants with imputed values |
| Daily Emollient | Atopic Dermatitis With or Without Prescription or Over-the-counter Therapies in Chart (Ordinal) | Atopic dermatitis with prescription therapy | 78.2 Participants with imputed values |
| Natural Skin | Atopic Dermatitis With or Without Prescription or Over-the-counter Therapies in Chart (Ordinal) | Atopic dermatitis with prescription therapy | 120.1 Participants with imputed values |
| Natural Skin | Atopic Dermatitis With or Without Prescription or Over-the-counter Therapies in Chart (Ordinal) | No atopic dermatitis | 356.5 Participants with imputed values |
| Natural Skin | Atopic Dermatitis With or Without Prescription or Over-the-counter Therapies in Chart (Ordinal) | Atopic dermatitis with over-the-counter therapy | 59.7 Participants with imputed values |
| Natural Skin | Atopic Dermatitis With or Without Prescription or Over-the-counter Therapies in Chart (Ordinal) | Atopic dermatitis without topical medication | 88.7 Participants with imputed values |
Comparison: The null hypothesis is that the odds of belonging to the next higher category of severity are equal in the Daily Emollient and Natural Skin arms.p-value: 0.00495% CI: [0.55, 0.89]Regression, proportional odds
Secondary
Atopic Dermatitis With Prescription or Over-the-counter Therapies in Chart
Cumulative incidence of provider-diagnosed AD requiring prescription or over-the-counter therapies from chart review. Health records at primary care practice includes both a diagnosis of AD and prescription and/or over-the-counter (OTC) therapies. Prescription therapies could be steroids, calcineurin inhibitors, crisaborole, or antibacterials. OTC therapies could be steroids or antihistamines.
Time frame: up to 24 months
Population: Multiple imputation of 199 missing outcomes. All ITT with multiple imputation for 16% of participants with absent outcome data. Numbers represent participants according to arm randomized, regardless of adherence to study instructions. Counts were summarized over 15 multiple imputation datasets generated by chained equations using baseline and follow-up survey responses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daily Emollient | Atopic Dermatitis With Prescription or Over-the-counter Therapies in Chart | 116.5 Participants with imputed values |
| Natural Skin | Atopic Dermatitis With Prescription or Over-the-counter Therapies in Chart | 179.8 Participants with imputed values |
Comparison: The null hypothesis is that the cumulative incidence of AD with prescription or OTC therapies in the health record does not differ between the Daily Emollient and Natural Skin arms, or that the risk ratio (RR) is equal to 1.p-value: 0.000495% CI: [0.55, 0.84]Regression, log-binomial
Secondary
Food Allergy Diagnosis With Positive Test
Parent reports a provider diagnosis of and a positive test for food allergy at 12- or 24-month questionnaire, or both.
Time frame: up to 24 months
Population: Respondents who answered items about immediate food allergy symptoms. Numbers represent participants according to arm randomized, regardless of adherence to study instructions.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daily Emollient | Food Allergy Diagnosis With Positive Test | 16 participants |
| Natural Skin | Food Allergy Diagnosis With Positive Test | 18 participants |
Comparison: The null hypothesis is that the cumulative incidence of food allergies does not differ between the Daily Emollient and Natural Skin arms, or that the risk ratio (RR) is equal to 1.p-value: 0.66995% CI: [0.45, 1.66]Regression, log-binomial
Secondary
Food Allergy Symptoms
Parent reports immediate food allergy reaction in child at 12- or 24-month questionnaire, or both.
Time frame: 12 months, 24 months or both
Population: Respondents who answered items about immediate food allergy symptoms. Numbers represent participants according to arm randomized, regardless of adherence to study instructions.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daily Emollient | Food Allergy Symptoms | 59 participants |
| Natural Skin | Food Allergy Symptoms | 77 participants |
Comparison: The null hypothesis is that the cumulative incidence of immediate food allergy reactions does not differ between the Daily Emollient and Natural Skin arms, or that the risk ratio (RR) is equal to 1.p-value: 0.07995% CI: [0.55, 1.03]Regression, log-binomial
Secondary
Parent Report of Atopic Dermatitis
Parent or guardian reports that a clinician has diagnosed their child with atopic dermatitis (eczema) at any quarterly contact up to 24 months of age.
Time frame: up to 24 months
Population: Multiple imputation of 111 outcomes considered missing when parent did not respond at 21 or 24 months and no diagnosis had been reported at earlier contacts. All ITT with multiple imputation for 9% of participants with absent outcome data. Numbers represent participants according to arm randomized, regardless of adherence to study instructions. Counts were summarized over 15 multiple imputation datasets generated by chained equations using baseline and follow-up survey responses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daily Emollient | Parent Report of Atopic Dermatitis | 161.1 Participants with imputed values |
| Natural Skin | Parent Report of Atopic Dermatitis | 219.1 Participants with imputed values |
Comparison: The null hypothesis is that the cumulative incidence of parent-reported AD does not differ between the Daily Emollient and Natural Skin arms, or that the risk ratio (RR) is equal to 1.p-value: 0.00295% CI: [0.65, 0.9]Regression, log-binomial
Secondary
Prescribed or Over-the-counter Topical Skin Medication by Parent Report
Ordinal formulation of parent report: no AD, AD not treated with steroidal or non-steroidal cream or ointment (therapy), AD treated with over-the-counter (OTC) therapy, AD treated with prescription therapy. AD could be reported on annual questionnaires or quarterly contacts. Therapies reported on annual questionnaires.
Time frame: up to 24 months
Population: Participants with (a) a parent report of provider diagnosis from an annual questionnaire or quarterly contact or (b) if no diagnosis, a parent response to a quarterly or annual contact at 21 to 24 months. Numbers represent participants according to arm randomized, regardless of adherence to study instructions.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Daily Emollient | Prescribed or Over-the-counter Topical Skin Medication by Parent Report | OTC topical | 31 participants |
| Daily Emollient | Prescribed or Over-the-counter Topical Skin Medication by Parent Report | AD, no topical OTC or Rx reported | 36 participants |
| Daily Emollient | Prescribed or Over-the-counter Topical Skin Medication by Parent Report | Rx and/or OTC topical | 84 participants |
| Daily Emollient | Prescribed or Over-the-counter Topical Skin Medication by Parent Report | No AD | 410 participants |
| Natural Skin | Prescribed or Over-the-counter Topical Skin Medication by Parent Report | Rx and/or OTC topical | 102 participants |
| Natural Skin | Prescribed or Over-the-counter Topical Skin Medication by Parent Report | OTC topical | 38 participants |
| Natural Skin | Prescribed or Over-the-counter Topical Skin Medication by Parent Report | No AD | 364 participants |
| Natural Skin | Prescribed or Over-the-counter Topical Skin Medication by Parent Report | AD, no topical OTC or Rx reported | 52 participants |
Comparison: The null hypothesis is that the odds of belonging to the next higher category of severity are equal in the Daily Emollient and Natural Skin arms.p-value: 0.01395% CI: [0.56, 0.93]Regression, proportional odds
Secondary
Primary Outcome of Provider-diagnosed Atopic Dermatitis
Diagnosis of atopic dermatitis (eczema) recorded by primary care providers in health records up to 12 months of age (rather than 24 months).
Time frame: up to 12 months
Population: Infants with diagnosis of atopic dermatitis at \<=12 months or with no diagnosis and at least one primary care visit in the health record after 9 months of age. Numbers represent participants according to arm randomized, regardless of adherence to study instructions.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Daily Emollient | Primary Outcome of Provider-diagnosed Atopic Dermatitis | 115 Participants |
| Natural Skin | Primary Outcome of Provider-diagnosed Atopic Dermatitis | 151 Participants |
Comparison: The null hypothesis is that the cumulative incidence of AD does not differ between the Daily Emollient and Natural Skin arms, or that the risk ratio (RR) is equal to 1. Alternatively, a RR \< 1 could be considered evidence that daily emollient is associated with lower incidence of AD.p-value: 0.01395% CI: [0.62, 0.95]Regression, log-binomial
Secondary
Provider-diagnosed Asthma
Health records at primary care practice include at least one diagnosis of asthma.
Time frame: up to 24 months
Population: All participants with (a) at least one primary care visit between 20 and 27 months of age or (b) asthma diagnosis earlier than 20 months. Numbers represent participants according to arm randomized, regardless of adherence to study instructions.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daily Emollient | Provider-diagnosed Asthma | 14 participants |
| Natural Skin | Provider-diagnosed Asthma | 13 participants |
Comparison: The null hypothesis is that the cumulative incidence of asthma in the health record does not differ between the Daily Emollient and Natural Skin arms, or that the risk ratio (RR) is equal to 1.p-value: 0.995% CI: [0.5, 2.18]Regression, log-binomial
Secondary
Provider-diagnosed Atopic Dermatitis at 18 Months
Diagnosis of atopic dermatitis (eczema) recorded by primary care providers in health records up to 18 months of age.
Time frame: up to 18 months
Population: Infants with diagnosis of atopic dermatitis at \<=18 months or with no diagnosis and at least one primary care visit in the health record after 15 months of age. Numbers represent participants according to arm randomized, regardless of adherence to study instructions.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Daily Emollient | Provider-diagnosed Atopic Dermatitis at 18 Months | 154 Participants |
| Natural Skin | Provider-diagnosed Atopic Dermatitis at 18 Months | 196 Participants |
Comparison: The null hypothesis is that the cumulative incidence of AD does not differ between the Daily Emollient and Natural Skin arms, or that the risk ratio (RR) is equal to 1. Alternatively, a RR \< 1 could be considered evidence that daily emollient is associated with lower incidence of AD.p-value: 0.00995% CI: [0.67, 0.94]Regression, log-binomial
Secondary
Severity of AD Symptoms Using IDQoL
Symptom severity as reflected by the Infant Dermatology Quality of Life Instrument (IDQoL) elicited from families of infants who reported AD diagnosis at this or any previous contact or whose CEQ response indicated AD. The IDQoL has 12 items and ranges from 0-37 with higher scores reflecting greater adverse effect of AD on quality of life
Time frame: 12 months
Population: Respondents to 12-month questionnaires who reported a provider diagnosis of AD in the same questionnaire or at a quarterly contact, or whose response to the CEQ indicated AD. Numbers represent participants according to arm randomized, regardless of adherence to study instructions.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Daily Emollient | Severity of AD Symptoms Using IDQoL | 4 score on a scale |
| Natural Skin | Severity of AD Symptoms Using IDQoL | 4 score on a scale |
Comparison: The null hypothesis is that the odds of belonging to the next higher category of severity are equal in the Daily Emollient and Natural Skin arms, or that the ordinal odds ratio (OR) is equal to 1.p-value: 0.0795% CI: [0.97, 2.18]Regression, proportional odds
Secondary
Severity of AD Symptoms Using IDQoL
Symptom severity as reflected by the Infant Dermatology Quality of Life Instrument (IDQoL) elicited from families of infants who reported AD diagnosis at this or any previous contact or whose CEQ response indicated AD. The IDQoL has 12 items and ranges from 0-37 with higher scores reflecting greater adverse effect of AD on quality of life
Time frame: 24 months
Population: Respondents to 24-month questionnaires who reported a provider diagnosis of AD in the same questionnaire or at a quarterly contact, or whose response to the CEQ indicated AD. Numbers represent participants according to arm randomized, regardless of adherence to study instructions.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Daily Emollient | Severity of AD Symptoms Using IDQoL | 3 score on a scale |
| Natural Skin | Severity of AD Symptoms Using IDQoL | 3 score on a scale |
Comparison: The null hypothesis is that the odds of belonging to the next higher category of severity are equal in the Daily Emollient and Natural Skin arms, or that the odds ratio (OR) is equal to 1. An OR \< 1 could be considered evidence that daily emollient use is associated with lower severity of AD symptoms among those diagnosed with AD.p-value: 0.08595% CI: [0.96, 1.91]Regression, proportional odds
Secondary
Severity of AD Symptoms Using POEM
Patient-Oriented Eczema Measure (POEM) score, elicited from families of infants who reported AD diagnosis at this or any previous contact or whose CEQ response indicated AD. The POEM has seven items and ranges from 0 to 28, with higher scores reflecting more severe symptoms of AD.
Time frame: 12 months of age
Population: Respondents to 12-month questionnaires who reported a provider diagnosis of AD in the same questionnaire or at a quarterly contact, or whose response to the CEQ indicated AD. Numbers represent participants according to arm randomized, regardless of adherence to study instructions.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Daily Emollient | Severity of AD Symptoms Using POEM | 3 score on a scale |
| Natural Skin | Severity of AD Symptoms Using POEM | 2 score on a scale |
Comparison: The null hypothesis is that the odds of belonging to the next higher category of severity are equal in the Daily Emollient and Natural Skin arms, or that the ordinal odds ratio (OR) is equal to 1.p-value: 0.06495% CI: [0.98, 2.21]Regression, proportional odds
Secondary
Severity of AD Symptoms Using POEM
Patient-Oriented Eczema Measure (POEM) score, elicited from families of infants who reported AD diagnosis at this or any previous contact or whose CEQ response indicated AD. The POEM has seven items and ranges from 0 to 28, with higher scores reflecting more severe symptoms of AD.
Time frame: 24 months of age
Population: Respondents to 24-month questionnaires who reported a provider diagnosis of AD in the same or previous annual questionnaire or at a quarterly contact, or whose response to the CEQ indicated AD. Numbers represent participants according to arm randomized, regardless of adherence to study instructions.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Daily Emollient | Severity of AD Symptoms Using POEM | 2 score on a scale |
| Natural Skin | Severity of AD Symptoms Using POEM | 1 score on a scale |
Comparison: The null hypothesis is that the odds of belonging to the next higher category of severity are equal in the Daily Emollient and Natural Skin arms, or that the ordinal odds ratio (OR) is equal to 1.p-value: 0.00795% CI: [1.14, 2.3]Regression, proportional odds
Secondary
Skin Infections Diagnosed and Recorded in Chart Review
Chart outcome for provider diagnosis or medications associated with skin infections, including topical antibiotics. Skin infection diagnoses include impetigo, candida, wart/verruca, molluscum, or herpes simplex.
Time frame: up to 24 months
Population: All participants with (a) at least one primary care visit between 20 and 27 months of age or (b) a skin infection diagnosis earlier than 20 months. Numbers represent participants according to arm randomized, regardless of adherence to study instructions.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Daily Emollient | Skin Infections Diagnosed and Recorded in Chart Review | 101 Participants |
| Natural Skin | Skin Infections Diagnosed and Recorded in Chart Review | 107 Participants |
Comparison: The null hypothesis is that the cumulative incidence of skin infections in the health record does not differ between the Daily Emollient and Natural Skin arms.p-value: 0.50995% CI: [0.73, 1.17]Regression, log-binomial
Other Pre-specified
Provider-diagnosed Atopic Dermatitis - High-risk Population
Subgroup population: In the subgroup of participants who reported atopic dermatitis in a first-degree relative, diagnosis of atopic dermatitis (eczema) recorded by primary care providers in health records
Time frame: up to 24 months
Population: All ITT with multiple imputation for 13% of participants with absent outcome data. Numbers represent participants according to arm randomized, regardless of adherence to study instructions. Counts were summarized over 15 multiple imputation datasets generated by chained equations using baseline and follow-up survey responses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daily Emollient | Provider-diagnosed Atopic Dermatitis - High-risk Population | 115.7 Participants with imputed values |
| Natural Skin | Provider-diagnosed Atopic Dermatitis - High-risk Population | 128.7 Participants with imputed values |
Comparison: The null hypothesis is that the cumulative incidence of AD does not differ between the Daily Emollient and Natural Skin arms, or that the risk ratio (RR) is equal to 1.p-value: 0.30395% CI: [0.73, 1.1]Regression, log-binomial
Other Pre-specified
Provider-diagnosed Atopic Dermatitis - Low-risk Population
Subgroup population: In the subgroup of participants who did not report atopic dermatitis in a first-degree relative, diagnosis of atopic dermatitis (eczema) recorded by primary care providers in health records
Time frame: up to 24 months
Population: All ITT with multiple imputation for 19% of participants with absent outcome data. Numbers represent participants according to arm randomized, regardless of adherence to study instructions. Counts were summarized over 15 multiple imputation datasets generated by chained equations using baseline and follow-up survey responses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daily Emollient | Provider-diagnosed Atopic Dermatitis - Low-risk Population | 102.1 Participants with imputed values |
| Natural Skin | Provider-diagnosed Atopic Dermatitis - Low-risk Population | 139.7 Participants with imputed values |
Comparison: The null hypothesis is that the cumulative incidence of AD does not differ between the Daily Emollient and Natural Skin arms, or that the risk ratio (RR) is equal to 1.p-value: 0.01295% CI: [0.63, 0.94]Regression, log-binomial